Two photon PDT

New advances in PDT include (1) metronomic PDT, in which the photosensitizer and light are delivered at a very low dose rate over extended periods (2) two-photon PDT, with activation being realized either through simultaneous absorption of two low-energy photons (near infrared) or by a sequential absorption (excitation... 

In addition, two-photon excitation can be another effective way to achieve NIR-triggered PDT/PTT synergistic therapy. For example, Li and coworkers also prepared hypocrellin-loaded AuNCs for two-photon PDT/PTT of cancer. The AuNCs were optimized to have efficient NIR absorption and further coated with lipids containing hydrophobic photosensitizer hypocrellin B (HB). The photodynamic effect of the photosensitizer was quenched in the Au nanostructure, thereby reducing side effects of the photosensitizer in unintended locations. For in vitro experiments, cancer cells were treated with the nanocomplex and irradiated with a 790 nm pulsed NIR laser. The photosensitizer HB was released from the AuNCs in the intracellular region, which induced dramatic phototoxicity due to the synergistic effect of PDT and PTT under two-photon irradiation. 

The photophysical properties of magnesium(II) tetra-(i-butyl)phthalocyanine (27) have been studied in solution, in micelles and in liposomes cation radical formation (CBr4 as electron acceptor) has been detected with UV excitation, or by a two-photon excitation using a pulsed laser in the therapeutic window at 670 nm.118 The Mg11 complex of octa(tri-z -propylsilylethy-nyl)tetra[6,7]quinoxalinoporphyrazine (28) has been prepared as a potential PDT sensitizer. The synthesis is shown in Figure 8. Compound (28) has Amax 770 nm (e = 512,000 M-1 cm-1), d>f = 0.46 and d>A = 0.19 (all in THF, under air).119... 

Figure 17.8 Two-photon photodynamic therapy (PDT) (a) simultaneous absorption of two near-infrared (NIP) photons raises the sensitizer to the S, excited state (b) sequential absorption of two photons, one from S0 and the other from T, raises the sensitizer to a higher excited state...

The other important development, based on the fact that the ROS diffusion distance is limited to hundreds of nanometres, utilises the fact that the irradiated volume in PDT can be as small as 1 pm, when femtosecond pulsed lasers are used as an excitation source. Precise localisation of excitation light should, in principle, allow the treatment of tissues without any damage to surrounding structures, which is crucial in the treatment of sensitive tissues such as those found in the eye and the brain of the patient. See Sect. 9.11 for more details of this emerging treatment modality two-photon excited PDT (TPE PDT). 

Of particular interest for us here is the utilisation of multiphoton processes requiring high energy pulses. Such multiphoton processes have caused much excitement in the last decade and offered novel solutions for biological and medical applications, in particular, multiphoton imaging and two-photon excited PDT (TPE PDT) [28, 29]. 

Similarly to TPE PDT, intense laser hght can be used in two-photon laser ablation of tissues, termed nanosurgery. The major benefit of using femtosecond laser pulses for nanosurgery is high peak intensities that reduce the energy threshold for tissue removal (ablation) and enable laser ablation to proceed with a low-energy... 

Light is a versatile physical stimulus that can be localized with optical fibers whose penetration can be tuned using UV, near infrared (NIR) or two-photon sources. Photoresponsive polymers contain groups that aggregate or are cleaved after irradiation (for a recent review see [ 141 ]). Whereas the photoresponsive groups (photosensitizers) have minimal toxicity themselves, irradiation leads to generation of reactive oxygen species and cell death (photodynamic therapy, PDT). 

Novel triad PDT agent - two photon excited photosensitizer with targeting and imaging agents... 

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